Cortical potentials evoked by stimulation of cervical vagus vs. auricular nerve: a comparative, parametric study in nonhuman primates

Figures

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  Figure 1.. Experimental cortical and vagus nerve implant. (A) Schematic illustration of the dual-electrode implant system with 3 mm and 5 mm rods penetrating the brain. (B) Locations of implanted electrodes on the cortical map. (C) Schematic representation of the electrical stimulation parameters used to generate the protocols investigated in the study. (D) Ear clip used to non-invasively stimulate the auricular branch of the vagus nerve (taNS). (E) Schematic illustration of the location of the stimulated areas for taNS, cVNS and trans-auricular control (taCON). For cVNS the dual helical stimulating cuff was wrapped around the vagus nerve. Created in BioRender. Rembado, I. (2026) https://BioRender.com/b8tkx6h

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  Figure 2.. Processing and characterization of vagal evoked potentials (VEPs). (A) Shown are stimulus-evoked potentials across all recording sites in left SM area (colored lines); by averaging across the sites, the SM area-specific vagal-evoked potential (VEP) is calculated, followed by smoothing (black trace). Several features are extracted from the VEP, specifically, the latency and amplitude of waves with amplitudes exceeding three standard deviations above the mean of pre-stimulus baseline. In this example, 3 waves are detected, at 3 different latencies (early, intermediate and late). Stimulation parameters used in this example are shown in the top-right. Note that the absolute value of the amplitude of the detected waves was used in statistical analyses. (B) Distribution of number of waves detected in single VEPs, across all animals and stimulation protocols (6,502 waves from 4,048 VEPs). (C) Distribution of latencies of the detected waves. Based on this distribution, we defined waves occurring 30–100 ms post-stimulus as Early Component (EC), 101–200 ms as Intermediate Component (IC) and 201–500 ms as Late Component (LC). The overall shape of the latency distribution was similar in…

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  Figure 3.. VEPs elicited by cVNS vs. taNS. (A) Example VEPs elicited by taNS (blue trace) and by cVNS (red trace), of similar stimulation parameters (shown in the top-right); marked are detected early, intermediate and late components (EC, red; IC, blue; LC, green symbols, respectively). (B) Adjusted means (± SEM) for EC, IC and LC amplitude, across all animals and stimulation parameters, for taNS vs. cVNS. (C) Adjusted means for EC, IC and LC latency, across all animals and stimulation parameters, for taNS vs. cVNS.

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  Figure 4.. Effects of stimulation parameters on amplitude of the early component (EC) of VEPs. (A) Adjusted mean values (± SEM) of EC amplitude for taNS and cVNS at different brain areas. (B) Adjusted mean values for taNS and cVNS for different stimulation frequencies. (C) Adjusted mean values for taNS and cVNS for different pulse widths. (D) Adjusted mean values for taNS and cVNS for ipsilateral and contralateral stimulation. (E) Adjusted mean values for taNS and cVNS for different pulse counts. (F) Adjusted mean values for taNS and cVNS for different current intensities. In all the plots taNS is shown with empty circles and cVNS with filled circles.

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  Figure 5.. Effects of stimulation parameters on latency of the early component (EC) of VEPs. (A)-(F) Same as Fig. 4, but for EC latency.

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  Figure 6.. Effects of stimulation parameters on the amplitude of the intermediate component (IC) of VEPs. (A-F) Same as Fig. 4, but for the amplitude of the IC.

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  Figure 7.. Effects of stimulation parameters on the latency of the intermediate component (IC) of VEPs. (A-F): Same as Fig. 4, but for the latency of the IC.

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  Figure 8.. Effects of stimulation parameters on the amplitude of the late component. (A-F): Same as Fig. 4, but for the amplitude of the LC.

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  Figure 9.. Effects of stimulation parameters on the latency of the late component (LC) of VEPs. (A-F): Same as Fig. 4, but for the latency of the LC.